Oberst has also been heavily influenced by the 1960s folk revival, mentioning Neil Young, Leonard Cohen, and country Singers Emmylou Harris, John Prine and Townes Van Zandt. As a strong musician in the folk genre, he is sometimes considered "a new Bob Dylan." He covered Neil Young's "Out on the Weekend", collaborating with Mike Mogis, Jim James and M. Ward in concert. He performed the Townes Van Zandt song "Rex's Blues" live with fellow musician Steve Earle. He has also performed two of John Prine's songs live, "Crazy as a Loon" and "Wedding Day in Funerville". Harris sang on a few tracks on Bright Eyes' I'm Wide Awake, It's Morning.

Conor Mullen Oberst was born on February 15, 1980, as the youngest in a family of three boys, and raised in Omaha, Nebraska, to Matthew Ryan Oberst, Sr., an information manager for Mutual of Omaha, and Nancy Oberst, an elementary education Director for Omaha Public Schools. Oberst has two elder brothers, Matthew Ryan Oberst, Jr. and Justin H. Oberst. Matthew was a Teacher & part-time musician, and helped Finance one of Oberst's self-released independent albums. Matt was also in the indie band Sorry About Dresden, which Conor played in from time to time. Justin H. Oberst is a graduate of the University of Nebraska College of Law and managing partner of a law firm.

One night in 1992, Ted Stevens (of Mayday and Cursive) invited Oberst onstage to play. Bill Hoover, who was in attendance, invited Oberst to come back to play with him a couple of weeks later. In that short amount of time, Oberst wrote enough songs to fill out the set, establishing himself as an Artist. Shortly thereafter, Oberst began committing his new repertoire to tape in his parents' basement with his father's four track cassette recorder and an acoustic guitar.

In mid-1993, Oberst self-released his debut album Water on cassette tape. The release of the album was financed by his brother Justin on what they called Lumberjack Records, the indie label that would become Saddle Creek Records, making them founders and present day executives of the label.

Oberst formed the rock band Commander Venus in 1994 with Tim Kasher, Ben Armstrong, and Robb Nansel. They recorded two albums: Do You Feel at Home? (1995) and The Uneventful Vacation (1997). Kasher later went on to form Cursive and Nansel was the co-founder of Saddle Creek Records. Kasher left the group to focus on Cursive as they were about to go into the studio to record their second album, and was replaced by Todd Baechle. Commander Venus disbanded in 1998.

Oberst founded Bright Eyes as a solo project in 1995, and after the disbanding of Commander Venus, released A Collection of Songs Written and Recorded 1995-1997 in January 1998. This was followed quickly by Letting Off the Happiness, released in November of the same year. It featured members of numerous bands and was recorded in the Oberst family basement. One year later, Bright Eyes released its first EP, Every Day and Every Night. Bright Eyes' third album, Fevers and Mirrors was released in May 2000; it was ranked 170 on Pitchfork's list of the top 200 albums of the 2000s.

In January 1996, Oberst began playing drums in a group named Park Ave., alongside Clark Baechle, Jenn Bernard, Neely Jenkins (now in the band Tilly and the Wall), and Jamie Williams (also in Tilly and the Wall). The group only played between 10 and 15 shows and made a handful of recordings (several of them with Mike Mogis as producer). The group disbanded in 1998 when Williams, the singer and primary Songwriter, moved to London, England. In 1999, Urinine Records released their only album, When Jamie Went to London...We Broke Up, which has also now been re-released under Team Love.

Oberst is a Guitarist and singer for Desaparecidos. The music and lyrics of Desaparecidos differ greatly from Bright Eyes, having more in Common with punk rock than Oberst's usual folk rock. The lyrics are generally social commentary on the state of affairs in America and the pitfalls of the suburban lifestyle, as opposed to the more introspective lyrics of Bright Eyes. Desaparecidos was active as a band between 2001–2002 but have regrouped to play shows in the Omaha area. They had two releases in 2002: a single for "The Happiest Place on Earth" and the full-length Read Music / Speak Spanish, on Saddle Creek Records.

Oberst was also greatly influenced by Daniel Johnston, whose "Devil Town" was covered and featured on Noise Floor, and profoundly influenced by Elliott Smith, stating in an October 22, 2003 All Things Considered interview that, "sometimes when you're not feeling good, you have to Listen to really sad music like Elliott Smith's" and that [Smith] "wrote the sweetest, saddest, most gentle songs". Oberst also said he liked to "listen to Elliott Smith's songs when he [couldn't] find anyone to talk to on the phone" and thought that it was sad that "through his music, [Smith] had the ability to answer feelings in others that he was unable to answer in himself". A live cover of Smith's "The Biggest Lie" is featured on Motion Sickness.

With the release of 2002's Lifted or The Story Is in the Soil, Keep Your Ear to the Ground, Bright Eyes received national attention and Oberst was proclaimed a breakthrough Artist by several notable magazines. On January 25, 2005 Bright Eyes simultaneously released two new albums: the folk I'm Wide Awake, It's Morning and more electronic-pop Digital Ash in a Digital Urn. Time listed I'm Wide Awake, It's Morning as one of the top ten albums of 2005.

In November 2007, it was reported that Oberst would work on a solo record with Jake Bellows, and that he and M. Ward would start a band and perform two late December shows in Minneapolis, Minnesota. Contrary to what was believed, the shows were not played with M. Ward, but rather with Nik Freitas and Jason Boesel. They also played a show in February in Mexico City, Mexico.

Conor Oberst released the self-titled album Conor Oberst, which was recorded in Tepoztlán, Morelos, Mexico with Taylor Hollingsworth on guitar and Macey Taylor on bass, on August 5, 2008 on Merge Records.

Conor Oberst is one of the four members of the band Monsters of Folk. Other band members include Jim James of My Morning Jacket, M. Ward and fellow Bright Eyes member Mike Mogis. The band members swap instruments and share vocal duties. The quartet released their self-titled debut album on September 22, 2009.

Oberst married Corina Figueroa Escamilla, whom he met while recording in Mexico, in 2010. His brother Matthew died suddenly in November 2016.

The Four Winds EP was released in March 2007, followed by their seventh album, Cassadaga in April. The song "Four Winds" was named a top 100 song of 2007 by Rolling Stone. Oberst spent the next two years focusing on other music projects, and in June 2009 told Rolling Stone he wanted to make one final album with Bright Eyes before retiring the group. The band subsequently released The People's Key on Conor's 31st birthday, February 15, 2011.

Oberst opened Pageturners Lounge with Philip Schaffart in 2012. Located in midtown Omaha, the lounge offers good beer, good wine, and premium well drinks. The Business name is a holdover from the bookstore that formerly occupied the space.

Oberst released a new solo record, titled Upside Down Mountain, on May 19, 2014. He has been working with Producer Jonathan Wilson (Dawes, Father John Misty) and Swedish duo First Aid Kit.

On October 28, 2015, it was announced that Conor Oberst had been hospitalized due to "laryngitis, anxiety, and exhaustion," according to a press release. The entirety of Desaparecidos' remaining tour dates were cancelled and Oberst returned to his hometown of Omaha to recuperate.

On October 14, 2016, Oberst released his seventh studio solo record, titled Ruminations, on Nonesuch Records.

On January 18, 2017, Oberst announced a companion album to Ruminations, called Salutations.